One aspect of the long-term exposure to toxins is significant alterations in patterns of gene expression. Toxin-related changes in gene regulation may contribute to the profile of illnesses caused by Superfund site toxicants, and can serve as a powerful marker of exposure and biohazard. In assessing hazards arising from Superfund sites, it would be highly desirable to develop cheap and rapid screens for the presence of environmental hazards, for the hazards posed by mixtures of toxins and to test large numbers of field isolates. To detect genes that are up- or down- regulated in response to toxins, we propose to use a gene-trapping approach with beta-lactamase as reporter in cell lines that are relevant to long-term toxicity. Cell lines in which beta-lactamase has trapped a toxin responsive gene will be used to identify trapped genes by RACE. Several tens of these cell lines will be validated for ultra-high-throughput screening assays to predict the biohazard potential of large numbers of samples (approximately 10/5 assays/day) consisting of candidate toxicants. mixtures, and field isolates.